Reciprocal Activation of Prostate Cancer Cells and Cancer-Associated Fibroblasts Stimulates Epithelial-Mesenchymal Transition and Cancer Stemness

Giannoni, Elisa; Bianchini, Francesca; Masieri, Lorenzo; Serni, Sergio; Torre, Eugenio; Calorini, Lido; Chiarugi, Paola

doi:10.1158/0008-5472.can-10-0785

Cited by 490 publications

(483 citation statements)

References 42 publications

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“…These cells formed more mammospheres and colonies in soft agar as compared to wild-type controls, and interestingly formed tumors when xenotransplanted in mice with a significantly higher efficiency suggesting that epithelial-to-mesenchymal transition indeed generated cells that fulfill most criteria used to define cancer stem cells (Mani et al, 2008). Similar data have since been presented for several other epithelial cancers such as prostate (Giannoni et al, 2010) …”

Section: B the Cancer Stem Cell Modelsupporting

confidence: 70%

Cancer Stem Cells in Tumor Heterogeneity

Pietras

2011

Advances in Cancer Research

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Section: B the Cancer Stem Cell Modelsupporting

confidence: 70%

Cancer Stem Cells in Tumor Heterogeneity

Pietras

2011

Advances in Cancer Research

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“…The relevance with FGF4 expression was analyzed by Pearson's w-square tests. Correlation coefficient between 18 We therefore examined whether fibroblasts can affect the tumorigenic capacity of CSCs/CICs of ovarian cancer cells. Ten thousand ALDH1 high cells with or without a mixture of normal skin fibroblasts (N25-5) were inoculated into NOD/SCID mice (Figure 2a).…”

Section: Discussionmentioning

confidence: 99%

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Yasuda

Torigoe

Mariya

et al. 2014

Laboratory Investigation

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Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tumorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/ CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1 high ) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1 high cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1 high cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1 high cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1 high cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as stemness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1 high cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1 high cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

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“…from at least three independent experiments, 27 and analysed by independentsamples t-test using the SPSS 13.0. software (SPSS). P-value less than 0.05 was considered significant.…”

Section: Discussionmentioning

confidence: 99%

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio-and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and b-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers. Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer in the oral cavity and is associated with high morbidity and poor prognosis. 1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood. 2,4 During metastatic progression, tumour cells lose cell-cell adhesion, detach from the primary site, invade the basement membrane, survive and circulate in the blood vessels, leave the bloodstream, and finally colonise in a new host environment to form micrometastases. 2,5-7 A growing body of research strongly suggests that the epithelial to mesenchymal transition (EMT), which occurs normally during embryonic development, tissue remodelling, and wound healing, is a critical early event in tumour invasion and metastasis. [8][9][10] It is characterised by downregulation of epithelial markers, such as E-cadherin, and upregulation of mesenchymal markers, such as vimentin. During the process of EMT, epithelial cells acquire mesenchymal cell properties and show reduced intercellular adhesion and increased invasion. 11 The transcriptional repressor Snail, which is a zinc finger protein, first described in Drosophila melanogaster, can bind to the E-boxes in the human E-cadherin promoter and suppress its transcription. 12,13 Snail has previously been implicated in triggering EMT during embryonic development, fibrosis, and tumour progression. 14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NB...

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Reciprocal Activation of Prostate Cancer Cells and Cancer-Associated Fibroblasts Stimulates Epithelial-Mesenchymal Transition and Cancer Stemness

Cited by 490 publications

References 42 publications

Cancer Stem Cells in Tumor Heterogeneity

Cancer Stem Cells in Tumor Heterogeneity

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

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